Comparing MCAS criteria to other conditions

library(tidyverse)
library(here)
library(vegan)
library(RColorBrewer)
library(broom)
source(here("util_functions.R"))

Read data

criteria_path <- here("data/disease_criteria")

parse_diagnoses <- function(sim_results){
  
  tibble(criteria = rownames(sim_results)) %>% 
    mutate(data = map(criteria, function(c){
      do.call(rbind, sim_results[c,]) %>% 
        mutate(diagnosis = map(diagnoses, process_diagnoses)) %>% 
        unnest(diagnosis) %>% 
        select(diagnosis)
      })) %>% 
    unnest(data)
         
}

# Read in ChatGPT output data for additional conditions and parse
df <- tibble(file = list.files(here("data/chatgpt_output/other_conditions"), full.names = T))%>% 
  mutate(data = map(file, readRDS)) %>% 
  mutate(data = map(data, parse_diagnoses)) %>% 
  unnest(data) %>% 
  select(-file)

# Read in original MCAS chatGPT output and append to data from additional conditions
df <- read_csv(here("data/compiled_mcas_chatgpt_diagnoses.csv")) %>% 
  mutate(criteria = gsub("consensus", "mcas_", consensus)) %>% 
  select(criteria, diagnosis) %>% 
  bind_rows(df) 

Rows: 38029 Columns: 2── Column specification ─────────────────────────────────────────────────────────────
Delimiter: ","
chr (2): diagnosis, consensus
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

df

# write_csv(df, here("data/compiled_all_chatgpt_diagnoses.csv"))
df <- read_csv(here("data/compiled_all_chatgpt_diagnoses.csv"))

Rows: 117354 Columns: 2── Column specification ─────────────────────────────────────────────────────────────────────────────
Delimiter: ","
chr (2): criteria, diagnosis
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

b <- df %>% count(diagnosis)

Plot distributions

# Rank abundance plot
custom_pal <- RColorBrewer::brewer.pal(7, "Set1")[-6]

df %>% 
  count(criteria, diagnosis, sort = T) %>% 
  group_by(criteria) %>% 
  mutate(freq = n/sum(n)) %>% 
  arrange(desc(freq), .by_group = T) %>% 
  mutate(rank = 1:n()) %>% 
  select(criteria, freq, rank) %>% 
  mutate(cs = cumsum(freq)) %>% 
  filter(rank <= 50) %>% 
  mutate(criteria = toupper(criteria)) %>% 
  ggplot(aes(x = rank, y = freq, color = factor(criteria)))+
    geom_line() +
    theme_classic()+
    scale_color_manual(values = custom_pal)+
  scale_x_continuous(expand = c(0,0))+
  scale_y_continuous(expand = c(0,0)) +
  labs(x = "Diagnosis rank", y = "Diagnosis frequency", color = "")

Calculate and plot diversity

# Calculate diversity values for diagnosis distributions
diagnosis_table <- table(df$criteria, df$diagnosis)
div_diag  <- vegan::diversity(diagnosis_table)
div_diag  

 aha_kawasaki eular_acr_sle        mcas_1        mcas_2      migraine     slicc_sle 
     4.768183      4.749758      4.847143      6.295376      4.134877      4.393290 

# Calculate similarity
plot_similarity <- function(d_method){
  broom::tidy(1-vegan::vegdist(diagnosis_table, method = d_method)) %>% 
    mutate(item = sprintf("%s_%s", item1, item2)) %>% 
    ggplot(aes(x = item, y = distance)) +
    geom_bar(stat = "identity")+
    theme_bw() +
    theme(axis.text.x = element_text(angle = 90, hjust = 1)) +
    coord_flip() +
    labs(x="", y="Similarity")
}

plot_similarity("bray")

(1-as.matrix(vegan::vegdist(diagnosis_table, method = "bray"))) %>%
  ComplexHeatmap::Heatmap(.,
                          name = "Similarity",
                          col = viridis::viridis(100))

diagnosis_pca <- as.data.frame(diagnosis_table) %>% 
  pivot_wider(names_from = "Var2", values_from = "Freq", values_fill = 0) %>% 
  column_to_rownames("Var1") %>% 
  prcomp()

as.data.frame(diagnosis_pca$x) %>% 
  rownames_to_column("criteria") %>% 
  ggplot(aes(x = PC1, y = PC2, label = criteria))+
  geom_label() +
  theme_bw()

# Plot diversity values
broom::tidy(div_diag) %>% 
  mutate(names = toupper(names)) %>% 
  ggplot(aes(x=names, y = x))+
  geom_bar(stat = "identity") +
  theme_bw() +
  labs(x = "", y = "Shannon diversity") +
  theme(axis.text.x = element_text(angle = 45, hjust = 1))

Warning: 'tidy.numeric' is deprecated.
See help("Deprecated")

Statistical testing

All group randomization

pairwise_div_difference <- function(df){
  df_div <- enframe(vegan::diversity(table(df$criteria, df$diagnosis)))
  df_diff <- data.frame(t(combn(unique(sort(df$criteria)),2))) %>% 
    left_join(df_div, by = c("X1"="name")) %>% 
    left_join(df_div, by = c("X2"="name")) %>% 
    unite("pair", X1, X2, sep = ".") %>%
    mutate(entropy_difference = value.x - value.y) %>% 
    select(-contains("value"))
  deframe(df_diff)
}

# pairwise_div_difference(df)
enframe(pairwise_div_difference(df), name = "pair", value = "entropy_difference")

pairwise_div_iteration <- function(){
  df %>% 
    count(criteria) %>% 
    mutate(diagnosis = map(n, function(x) sample(df$diagnosis, x, replace = T))) %>% 
    select(-n) %>% 
    unnest(diagnosis) %>% 
    pairwise_div_difference(.)
}

pairwise_div_iteration()

aha_kawasaki.eular_acr_sle        aha_kawasaki.mcas_1        aha_kawasaki.mcas_2 
              -0.008694848                0.008252266                0.012165368 
     aha_kawasaki.migraine     aha_kawasaki.slicc_sle       eular_acr_sle.mcas_1 
               0.002825259               -0.001106212                0.016947114 
      eular_acr_sle.mcas_2     eular_acr_sle.migraine    eular_acr_sle.slicc_sle 
               0.020860217                0.011520107                0.007588636 
             mcas_1.mcas_2            mcas_1.migraine           mcas_1.slicc_sle 
               0.003913103               -0.005427007               -0.009358478 
           mcas_2.migraine           mcas_2.slicc_sle         migraine.slicc_sle 
              -0.009340110               -0.013271581               -0.003931471 

set.seed(1234)
pairs_permutation_distributions <- data.frame(t(replicate(10000, pairwise_div_iteration())))

[WARNING] Deprecated: --self-contained. use --embed-resources --standalone

sapply(combn(unique(sort(df$criteria)),2, simplify = F), paste, collapse = ".")

 [1] "aha_kawasaki.eular_acr_sle" "aha_kawasaki.mcas_1"        "aha_kawasaki.mcas_2"       
 [4] "aha_kawasaki.migraine"      "aha_kawasaki.slicc_sle"     "eular_acr_sle.mcas_1"      
 [7] "eular_acr_sle.mcas_2"       "eular_acr_sle.migraine"     "eular_acr_sle.slicc_sle"   
[10] "mcas_1.mcas_2"              "mcas_1.migraine"            "mcas_1.slicc_sle"          
[13] "mcas_2.migraine"            "mcas_2.slicc_sle"           "migraine.slicc_sle"        

names(pairs_permutation_distributions)

 [1] "aha_kawasaki.eular_acr_sle" "aha_kawasaki.mcas_1"        "aha_kawasaki.mcas_2"       
 [4] "aha_kawasaki.migraine"      "aha_kawasaki.slicc_sle"     "eular_acr_sle.mcas_1"      
 [7] "eular_acr_sle.mcas_2"       "eular_acr_sle.migraine"     "eular_acr_sle.slicc_sle"   
[10] "mcas_1.mcas_2"              "mcas_1.migraine"            "mcas_1.slicc_sle"          
[13] "mcas_2.migraine"            "mcas_2.slicc_sle"           "migraine.slicc_sle"        

pairs_entropy_diff <- enframe(pairwise_div_difference(df), name = "pair", value = "entropy_difference") %>% 
  mutate(entropy_difference = ifelse(entropy_difference >=0, 0-entropy_difference, entropy_difference))
pairs_entropy_diff

read_csv(here("data/all_criteria_null_difference_distributions.csv")) %>% 
  # pivot_longer(everything(), names_to = "pair", values_to = "entropy_difference") %>% 
  ggplot(aes(x = entropy_difference)) +
  geom_histogram(binwidth = 0.01)+
  geom_vline(data = pairs_entropy_diff, aes(xintercept = entropy_difference), color = "red")+
  facet_wrap(~pair, scales = "free")+
  theme_classic()

Rows: 150000 Columns: 2── Column specification ─────────────────────────────────────────────────────────────
Delimiter: ","
chr (1): pair
dbl (1): entropy_difference
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

# Calculate p-values for diversity differences based on the quantile of the 
# diversity difference value compared to the null hypothesis diversity distribution values
# Pairwise comparison adjusted
entropy_diff_table <- read_csv(here("data/all_criteria_null_difference_distributions.csv"))  %>% 
  # pivot_longer(everything(), names_to = "pair", values_to = "entropy_difference") %>% 
  group_by(pair) %>% 
  summarise(entropy_difference_distribution = list(entropy_difference)) %>% 
  right_join(pairs_entropy_diff) %>% 
  mutate(p_value = map2_dbl(entropy_difference, entropy_difference_distribution, ~ecdf(.y)(.x))) %>% 
  mutate(p_adj = p.adjust(p_value, method = "bonferroni", n = n()))

Rows: 150000 Columns: 2── Column specification ─────────────────────────────────────────────────────────────
Delimiter: ","
chr (1): pair
dbl (1): entropy_difference
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.Joining with `by = join_by(pair)`

entropy_diff_table

# Plot diversity values
broom::tidy(div_diag) %>% 
  mutate(names = tolower(names)) %>% 
  ggplot(aes(x=names, y = x))+
  geom_bar(stat = "identity") +
  ggpubr::stat_pvalue_manual(
    entropy_diff_table %>% separate(pair, into = c("group1", "group2"), sep = "\\."),
    label= "p_adj",
    y.position = 7, step.increase = 0.2
  ) +
  theme_bw() +
  labs(x = "", y = "Shannon diversity") +
  theme(axis.text.x = element_text(angle = 45, hjust = 1))

Warning: 'tidy.numeric' is deprecated.
See help("Deprecated")

Pairwise randomization

pairs_list <- as.list(as.data.frame(combn(unique(df$criteria),2)))
names(pairs_list) <- sapply(pairs_list, paste, collapse = ".")
pairs_list

$mcas_1.mcas_2
[1] "mcas_1" "mcas_2"

$mcas_1.aha_kawasaki
[1] "mcas_1"       "aha_kawasaki"

$mcas_1.eular_acr_sle
[1] "mcas_1"        "eular_acr_sle"

$mcas_1.migraine
[1] "mcas_1"   "migraine"

$mcas_1.slicc_sle
[1] "mcas_1"    "slicc_sle"

$mcas_2.aha_kawasaki
[1] "mcas_2"       "aha_kawasaki"

$mcas_2.eular_acr_sle
[1] "mcas_2"        "eular_acr_sle"

$mcas_2.migraine
[1] "mcas_2"   "migraine"

$mcas_2.slicc_sle
[1] "mcas_2"    "slicc_sle"

$aha_kawasaki.eular_acr_sle
[1] "aha_kawasaki"  "eular_acr_sle"

$aha_kawasaki.migraine
[1] "aha_kawasaki" "migraine"    

$aha_kawasaki.slicc_sle
[1] "aha_kawasaki" "slicc_sle"   

$eular_acr_sle.migraine
[1] "eular_acr_sle" "migraine"     

$eular_acr_sle.slicc_sle
[1] "eular_acr_sle" "slicc_sle"    

$migraine.slicc_sle
[1] "migraine"  "slicc_sle"

# Create function that subsets df of all diagnoses for a criteria based on a pair of two criteria to compare
# Then randomizes the diagnoses across the two criteria, 
# measures the resulting diversity of each criteria's diagnoses
# and calculates a difference in the diversity value
# randomize can be set F to obtain original difference in diversity w/o randomization
# To be used with replicate to generate a null hypothesis distribution 
permutation_pair_iteration <- function(pair, randomize = T){
  df <- df %>% 
    filter(criteria %in% pair) 
  if (randomize == T){
    df <- df %>% mutate(diagnosis = sample(diagnosis, n()))
  }
  div <- vegan::diversity(table(df$criteria, df$diagnosis))
  unname(div[1] - div[2])
}

replicate(10,permutation_pair_iteration(pairs_list[[1]], randomize = T))

 [1]  0.0049722988  0.0081672943  0.0156799259  0.0038521584  0.0060045361 -0.0151564640
 [7]  0.0144935438 -0.0333420796  0.0278905935 -0.0006473075

replicate(10,permutation_pair_iteration(pairs_list[[1]], randomize = F))

 [1] -1.434911 -1.434911 -1.434911 -1.434911 -1.434911 -1.434911 -1.434911 -1.434911 -1.434911
[10] -1.434911

# # Create a null hypothesis distribution for the difference in diversity
# # For all pairs of criteria

# set.seed(1234)
# pairs_permutation_distributions <- lapply(pairs_list, function(x) replicate(10000, permutation_pair_iteration(x)))
# names(pairs_permutation_distributions) <- lapply(pairs_list, function(x) paste(x, collapse = "-"))
# data.frame(pairs_permutation_distributions)
# write_csv(data.frame(pairs_permutation_distributions), here("data/criteria_pairwise_null_difference_distributions.csv"))

pairs_permutation_distributions <- read_csv(here("data/criteria_pairwise_null_difference_distributions.csv"))

Rows: 10000 Columns: 15── Column specification ────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
Delimiter: ","
dbl (15): mcas_1.mcas_2, mcas_1.aha_kawasaki, mcas_1.eular_acr_sle, mcas_1.migraine, mcas_1.slicc_sle, mcas_2.aha_kawasaki, mcas_2.eular_acr_sle, mcas_2.migraine, mcas_2.slicc_sle, aha_kawasaki.eular_...
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.

pairs_permutation_distributions

# Create a df of the actual difference in diversity between pairs of criteria
pairs_entropy_diff <- lapply(pairs_list, permutation_pair_iteration, randomize = F)
names(pairs_entropy_diff) <- lapply(pairs_list, function(x) paste(x, collapse = "-"))
pairs_entropy_diff <- data.frame(pairs_entropy_diff) %>%  
  pivot_longer(everything(), names_to = "pair", values_to = "entropy_difference") %>% 
  mutate(entropy_difference = ifelse(entropy_difference >=0, 0-entropy_difference, entropy_difference))
pairs_entropy_diff

# Create plots of null hypothesis distributions, overlaid with actual diversity difference
read_csv(here("data/all_criteria_pairwise_null_difference_distributions.csv")) %>%
  group_by(pair) %>% 
  nest() %>% 
  separate(pair, into = c("p1","p2"), sep = "\\.", remove = F) %>%
  rowwise() %>% mutate(pair=paste(sort(c(p1,p2)), collapse = ".")) %>% 
  select(!pair:p2) %>% 
  unnest(data) %>% 
  # pivot_longer(cols = everything(), names_to = "pair", values_to = "entropy_difference") %>% 
  ggplot(aes(x = entropy_difference)) +
  geom_histogram(binwidth = 0.01)+
  geom_vline(data = pairs_entropy_diff, aes(xintercept = entropy_difference), color = "red")+
  facet_wrap(~pair, scales = "free")+
  theme_classic()

Rows: 150000 Columns: 2── Column specification ────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
Delimiter: ","
chr (1): pair
dbl (1): entropy_difference
ℹ Use `spec()` to retrieve the full column specification for this data.
ℹ Specify the column types or set `show_col_types = FALSE` to quiet this message.Adding missing grouping variables: `pair`

# Calculate p-values for diversity differences based on the quantile of the 
# diversity difference value compared to the null hypothesis diversity distribution values
# Pairwise comparison adjusted
data.frame(pairs_permutation_distributions) %>% 
  pivot_longer(everything(), names_to = "pair", values_to = "entropy_difference") %>% 
  group_by(pair) %>% 
  summarise(entropy_difference_distribution = list(entropy_difference)) %>% 
  right_join(pairs_entropy_diff) %>% 
  mutate(p_value = map2_dbl(entropy_difference, entropy_difference_distribution, ~ecdf(.y)(.x))) %>% 
  mutate(p_adj = p.adjust(p_value, method = "bonferroni", n = n()))

Joining with `by = join_by(pair)`

Plots